Mechanisms of climate change and related air pollution on the immune system leading to allergic disease and asthma.

Climate change is considered the greatest threat to global health. Greenhouse gases as well as global surface temperatures have increased causing more frequent and intense heat and cold waves, wildfires, floods, drought, altered rainfall patterns, hurricanes, thunderstorms, air pollution, and windstorms. These extreme weather events have direct and indirect effects on the immune system, leading to allergic disease due to exposure to pollen, molds, and other environmental pollutants. In this review, we will focus on immune mechanisms associated with allergy and asthma-related health risks induced by climate change events. We will review current understanding of the molecular and cellular mechanisms by which the changing environment mediates these effects.

Health Effects of Wildfire Smoke Exposure.

We review current knowledge on the trends and drivers of global wildfire activity, advances in the measurement of wildfire smoke exposure, and evidence on the health effects of this exposure. We describe methodological issues in estimating the causal effects of wildfire smoke exposures on health and quantify their importance, emphasizing the role of nonlinear and lagged effects. We conduct a systematic review and meta-analysis of the health effects of wildfire smoke exposure, finding positive impacts on all-cause mortality and respiratory hospitalizations but less consistent evidence on cardiovascular morbidity. We conclude by highlighting priority areas for future research, including leveraging recently developed spatially and temporally resolved wildfire-specific ambient air pollution data to improve estimates of the health effects of wildfire smoke exposure.

Cellular locomotion using environmental topography.

Eukaryotic cells migrate by coupling the intracellular force of the actin cytoskeleton to the environment. While force coupling is usually mediated by transmembrane adhesion receptors, especially those of the integrin family, amoeboid cells such as leukocytes can migrate extremely fast despite very low adhesive forces1. Here we show that leukocytes cannot only migrate under low adhesion but can also transmit forces in the complete absence of transmembrane force coupling. When confined within three-dimensional environments, they use the topographical features of the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton follows the texture of the substrate, creating retrograde shear forces that are sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent migration are not mutually exclusive, but rather are variants of the same principle of coupling retrograde actin flow to the environment and thus can potentially operate interchangeably and simultaneously. As adhesion-free migration is independent of the chemical composition of the environment, it renders cells completely autonomous in their locomotive behaviour.

Na+ controls hypoxic signalling by the mitochondrial respiratory chain.

All metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1-4, a phenomenon that occurs in hypoxia4-8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential10. Here we show that Na+ acts as a second messenger that regulates OXPHOS function and the production of reactive oxygen species by modulating the fluidity of the inner mitochondrial membrane. A conformational shift in mitochondrial complex I during acute hypoxia11 drives acidification of the matrix and the release of free Ca2+ from calcium phosphate (CaP) precipitates. The concomitant activation of the mitochondrial Na+/Ca2+ exchanger promotes the import of Na+ into the matrix. Na+ interacts with phospholipids, reducing inner mitochondrial membrane fluidity and the mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III. The inhibition of Na+ import through the Na+/Ca2+ exchanger is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences for cellular metabolism.

Climate change and public health: The effects of global warming on the risk of allergies and autoimmune diseases: The effects of global warming on the risk of allergies and autoimmune diseases.

Global climate change and extreme weather events are associated with epigenetic modifications in immune cells, leading to the possible increased risk and prevalence of allergies and autoimmune diseases.

A multi-modal wildfire prediction and early-warning system based on a novel machine learning framework.

Wildfires are increasingly impacting the environment and human health. Among the top 20 California wildfires, those in 2020-2021 burned more acres than the last century combined. Lack of an adequate early warning system impacts the health and safety of vulnerable populations disproportionately and widens the inequality gap. In this project, a multi-modal wildfire prediction and early warning system has been developed based on a novel spatio-temporal machine learning architecture. A comprehensive wildfire database with over 37 million data points was created, including the historical wildfires, environmental and meteorological sensor data from the Environmental Protection Agency, and geological data. The data was augmented into 2.53 km × 2.53 km square grids to overcome the sensor network coverage limitations. Leading and trailing indicators for the wildfires are proposed, classified, and tested. The leading indicators are correlated to the risks of wildfire conception, whereas the trailing indicators are correlated to the byproducts of the wildfires. Additionally, geological data was incorporated to provide additional information for better assessment on wildfire risks and propagation. Next, a novel U-Convolutional Long Short-Term Memory (ULSTM) neural network was developed to extract key spatial and temporal features of the dataset, specifically to address the spatial nature of the location of the wildfire and time-progression temporal nature of the wildfire evolution. Through iterative improvements and optimization, the final ULSTM network architecture, trained with data from 2012 to 2017, achieved >97% accuracy for predicting wildfires in 2018, as compared to ∼76% using traditional Convolutional Neural Network (CNN) techniques. The final model was applied to conduct a retrospective study for the 2018-2022 wildfire seasons, and successfully predicted 85.7% of wildfires >300 K acres in size. This technique could enable fire departments to anticipate and prevent wildfires before they strike and provide early warnings for at-risk individuals for better preparation, thereby saving lives, protecting the environment, and avoiding economic damages.

Climate Justice Is Environmental Justice: System Change for Promoting Planetary Health and a Just Transition From Extractive to Regenerative Action.

Our climate emergency is changing health promotion practice, and we need to increase our efforts. In the 20 years since our journal was published, we have witnessed the pressing challenges incurred by human-caused threats to planetary health. These threats are most profound in communities that are already unjustly under threat from structural factors such as poverty, toxic exposures, and inequitable allocation of resources for promoting their health. Those least responsible for contributing to this emergency, including all living environments in harm's way, will unjustly experience the greatest burdens. This commentary calls for health promotion practice to engage in system change and action in the struggle for climate justice by adopting a planetary health perspective. There must be a just transition from extractive to regenerative economies and actions. We describe our own journey as researchers and health practitioners toward this call for action. We propose a series of system change actions in social, environmental, political, health systems, and health profession education within the scope and responsibility of health promotion practice.

Climate change and global health: A call to more research and more action.

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political, and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study† ‡.

STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023.

Practical Strategies to Improve Your Writing: Lessons Learned From Public Health Practitioners Participating in a Writing Group.

Many public health professionals (researchers and practitioners) do not regularly spend time writing. We often receive no formal training in the practices that lead one to become a productive writer. In addition, many internal (mental/emotional) and external (schedules/distractions) barriers make writing consistently even less appealing and may lead to a cycle of avoidance followed by binge writing. This commentary demonstrates how one writing group became an effective means of providing career and professional development. Each week for 9 months we held a 1-hour writing group meeting designed around a commitment to ground rules, accountability, training opportunities, and feedback. Our experiences suggest that engaging in a writing group can help us develop as writers by allowing us to learn new practices and skills. Adopting new practices like writing regularly for short blocks of time, in turn, led to benefits like reduced anxiety and increased productivity. In the process, we became better writers, reviewers, and mentors. We provide recommendations and resources for groups and individuals who are interested in improving their writing as an essential component of their continuing education and professional development. Whatever your professional role, using a writing group to become a more powerful and productive writer will make you more effective.

Mitochondrial responsibility in ageing process: innocent, suspect or guilty.

Ageing is accompanied by the accumulation of damaged molecules in cells due to the injury produced by external and internal stressors. Among them, reactive oxygen species produced by cell metabolism, inflammation or other enzymatic processes are considered key factors. However, later research has demonstrated that a general mitochondrial dysfunction affecting electron transport chain activity, mitochondrial biogenesis and turnover, apoptosis, etc., seems to be in a central position to explain ageing. This key role is based on several effects from mitochondrial-derived ROS production to the essential maintenance of balanced metabolic activities in old organisms. Several studies have demonstrated caloric restriction, exercise or bioactive compounds mainly found in plants, are able to affect the activity and turnover of mitochondria by increasing biogenesis and mitophagy, especially in postmitotic tissues. Then, it seems that mitochondria are in the centre of metabolic procedures to be modified to lengthen life- or health-span. In this review we show the importance of mitochondria to explain the ageing process in different models or organisms (e.g. yeast, worm, fruitfly and mice). We discuss if the cause of aging is dependent on mitochondrial dysfunction of if the mitochondrial changes observed with age are a consequence of events taking place outside the mitochondrial compartment.

Bilayer Scaffolds of PLLA/PCL/CAB Ternary Blend Films and Curcumin-Incorporated PLGA Electrospun Nanofibers: The Effects of Polymer Compositions and Solvents on Morphology and Molecular Interactions.

Tissue engineering scaffolds have been dedicated to regenerating damaged tissue by serving as host biomaterials for cell adhesion, growth, differentiation, and proliferation to develop new tissue. In this work, the design and fabrication of a biodegradable bilayer scaffold consisting of a ternary PLLA/PCL/CAB blend film layer and a PLGA/curcumin (CC) electrospun fiber layer were studied and discussed in terms of surface morphology, tensile mechanical properties, and molecular interactions. Three different compositions of PLLA/PCL/CAB-60/15/25 (TBF1), 75/10/15 (TBF2), and 85/5/10 (TBF3)-were fabricated using the solvent casting method. The electrospun fibers of PLGA/CC were fabricated using chloroform (CF) and dimethylformamide (DMF) co-solvents in 50:50 and 60:40 volume ratios. Spherical patterns of varying sizes were observed on the surfaces of all blend films-TBF1 (17-21 µm) > TBF2 (5-9 µm) > TBF3 (1-5 µm)-caused by heterogeneous surfaces inducing bubble nucleation. The TBF1, TBF2, and TBF3 films showed tensile elongation at break values of approximately 170%, 94%, and 43%, respectively. The PLGA/CC electrospun fibers fabricated using 50:50 CF:DMF had diameters ranging from 100 to 400 nm, which were larger than those of the PLGA fibers (50-200 nm). In contrast, the PLGA/CC electrospun fibers fabricated using 60:40 CF:DMF had diameters mostly ranging from 200 to 700 nm, which were larger than those of PLGA fibers (200-500 nm). Molecular interactions via hydrogen bonding were observed between PLGA and CC. The surface morphology of the bilayer scaffold demonstrated adhesion between these two solid surfaces resembling "thread stitches" promoted by hydrophobic interactions, hydrogen bonding, and surface roughness.

Factors Associated with Neonatal Arterial Hypertension: Case and Control Study.

Background. Neonatal high blood pressure has been diagnosed more frequently in recent years, and its impact extends to adulthood. However, the knowledge gaps on associated factors, diagnosis, and treatment are challenging for medical personnel. The incidence of this condition varies depending on neonatal conditions. Patients in the Newborn Unit are at increased risk of developing high blood pressure. The persistence of this condition beyond the neonatal stage increases the risk of cardiovascular disease and chronic kidney disease in childhood and adulthood. Methodology. A case-control study was carried out. It included hospitalized patients with neonatal hypertension as cases. Three controls were randomly selected for each case and matched by gestational age. The variables were analyzed based on their nature. Multivariate analysis was performed using a multivariate conditional regression model to identify variables associated with the outcome. Finally, the model was adjusted for possible confounders. Results. 37 cases were obtained and matched with 111 controls. In the univariate analysis, heart disease (OR 2.86; 95% CI 1.22-6.71), kidney disease (OR 7.24; 95% CI 1.92-28.28), bronchopulmonary dysplasia (OR 6.62; 95% CI 1.42-50.82) and major surgical procedures (OR 3.71; 95% CI 1.64-8.39) had an association with neonatal arterial hypertension. Only the latter maintained this finding in the multivariate analysis (adjusted OR 2.88; 95% CI 1.14-7.30). A significant association of two or more comorbidities with neonatal arterial hypertension was also found (OR 3.81; 95% CI 1.53-9.49). Conclusions. The study analyzed the factors related to high blood pressure in hospitalized neonates, finding relevant associations in the said population. The importance of meticulous neonatal care and monitoring of risk factors such as birth weight and major surgeries is highlighted.

Diagnostic approach and monitoring of chronic kidney disease in the primary care pediatric population.

Chronic kidney disease (CKD) has severe consequences on the quality and expectancy of life and is considered a major health problem worldwide. This is, especially relevant in pediatric patients, as they have unique characteristics and a mortality rate 30 times higher (in advanced stages) than healthy people. This review aims to define the minimum components for the diagnostic approach and monitoring of CKD in the pediatric population from primary health care to promote comprehensive care and adequate risk management. For this purpose, we performed a systematic review of the literature with a panel of experts. Based on the evidence, to optimize the definition, diagnosis, and timely treatment of CKD in the pediatric population, we formulated 21 recommendations. These were approved by the research team and peer-reviewed by clinical experts. They will facilitate the definition of the diagnostic approach for CKD in the pediatric population in primary health-care settings, allowing for timely treatment intervention, comprehensive care, and monitoring of this disease.

La enfermedad renal crónica (ERC) tiene graves consecuencias en la calidad y la esperanza de vida, y se considera un importante problema de salud a nivel mundial. Esto es especialmente relevante en pacientes pediátricos, ya que presenta características únicas y una tasa de mortalidad en etapas avanzadas que es 30 veces mayor que en personas sanas. El objetivo de esta revisión fue definir los componentes mínimos para el abordaje diagnóstico y para el seguimiento de la ERC en la población pediátrica desde la atención primaria en salud, con el fin de promover la atención integral y una adecuada gestión del riesgo. Para esto, se realizó una revisión sistemática de la literatura con panel de discusión de expertos. Basándonos en la evidencia, y con el objetivo de optimizar la definición, diagnóstico y tratamiento oportuno de la ERC en la población pediátrica, se formularon 21 recomendaciones. Estas fueron aprobadas por el equipo desarrollador y los pares expertos clínicos evaluadores, y permitirán definir de manera oportuna el abordaje diagnóstico de la ERC en la población pediátrica desde la atención primaria en salud, facilitando la intervención temprana, una atención integral y el seguimiento de esta patología.

Metastatic lymphs nodes and lymph node ratio as predictive factors of survival in perforated and non-perforated T4 colorectal tumors.

AIMS: Recently it has been hypothesized that perforation of colorectal cancer (CRC) itself is not a predictor of poor prognosis. The aim of this study was to analyze the prognostic impact, of the spontaneous perforation of the tumour, metastatic lymph nodes and lymph node ratio (LNR) after potentially curative surgery. METHODS: Retrospective analysis of oncologic outcomes of patients with T4a CRC grouped by perforated and non-perforated tumours. Between 2001 and 2010, 100 patients were included. Oncologic outcomes, disease-free survival and global survival were analyzed. RESULTS: Forty-nine patients had a non-perforated cancer and 51 presented a perforated neoplasm. Perforated cancers had a lower mean number of lymph nodes (1.16 vs. 4.14, P < 0.001), lower LNR (0.13 vs. 0.33, P = 0.001), better TNM-stage (P < 0.001), and lower metastases during follows-up (P = 0.02). The perforated-group had higher survival (P = 0.017) and higher metastasis-free time (P = 0.03). LNR cutoffs (<0.05, 0.05-0.4, and >0.4) had significant differences in overall survival (log-rank < 0.001). The predictive value of LNR and metastatic lymph nodes in mortality was similar. CONCLUSIONS: In our experience, perforated cancers had higher survival rates and metastasis-free interval that non-perforated cancers, probably by a lower number of metastatic lymph nodes, smaller LNR and better TNM stage. Moreover the predictive value, in mortality rate, of metastatic lymph nodes and LNR was similar.

Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability.

PURPOSES: Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis by its role in DNA methylation, repair, and synthesis. We analyzed the impact of MTHFR C677T polymorphism in colorectal cancer in a region of the Tenerife Island whose population has a history of genetic isolation and a low genetic variability. This allows analyzing the effects of the polymorphism that are not due to interactions with different genetic variants. METHODS: Genomic DNA of 50 Spanish sporadic colorectal cancer (CRC) patients and 103 controls was analyzed by PCR/RFLP and sequencing. RESULTS: The T allele is more frequent in controls than in patients (P < 0.01). The variant (T) carriers displayed significant odds ratio values for the CT heterozygotes (P = 0.026) and even when grouping heterozygote (CT) and homozygotes (TT) (P = 0.015). Patients carriers of the variant T (CT y TT) show a higher survival rate after chemotherapy than the CC homozygotes (log rank; P = 0.001). CONCLUSIONS: The MTHRF C677T variant has a protective effect on CRC development in a population with low allelic variability and an optimal intake of folic acid. Moreover, patients carrying the variant (T) show a better prognosis after 5-fluorouracil/folinic acid-based chemotherapy.

Risk Factors for Bacteremia and Its Clinical Impact on Complicated Community-Acquired Urinary Tract Infection.

Bacteremia has been associated with severity in some infections; however, its impact on the prognosis of urinary tract infections (UTIs) is still disputed. Our goal is to determine the risk factors for bacteremia and its clinical impact on hospitalized patients with complicated community-acquired urinary tract infections. We conducted a prospective observational study of patients admitted to the hospital with complicated community-acquired UTIs. Clinical variables and outcomes of patients with and without bacteremia were compared, and multivariate analysis was performed to identify risk factors for bacteremia and mortality. Of 279 patients with complicated community-acquired UTIs, 37.6% had positive blood cultures. Risk factors for bacteremia by multivariate analysis were temperature ≥ 38 °C (p = 0.006, OR 1.3 (95% CI 1.1-1.7)) and procalcitonin ≥ 0.5 ng/mL (p = 0.005, OR 8.5 (95% CI 2.2-39.4)). In-hospital and 30-day mortality were 9% and 13.6%, respectively. Quick SOFA (p = 0.030, OR 5.4 (95% CI 1.2-24.9)) and Barthel Index <40% (p = 0.020, OR 4.8 (95% CI 1.3-18.2)) were associated with 30-day mortality by multivariate analysis. However, bacteremia was not associated with 30-day mortality (p = 0.154, OR 2.7 (95% CI 0.7-10.3)). Our study found that febrile community-acquired UTIs and elevated procalcitonin were risk factors for bacteremia. The outcomes in patients with bacteremia were slightly worse, but without significant differences in mortality.

Granzymes, IL-16, and poly(ADP-ribose) polymerase 1 increase during wildfire smoke exposure.

Background: Given the increasing prevalence of wildfires worldwide, understanding the effects of wildfire air pollutants on human health-particularly in specific immunologic pathways-is crucial. Exposure to air pollutants is associated with cardiorespiratory disease; however, immune and epithelial barrier alterations require further investigation. Objective: We sought to determine the impact of wildfire smoke exposure on the immune system and epithelial barriers by using proteomics and immune cell phenotyping. Methods: A San Francisco Bay area cohort (n = 15; age 30 ± 10 years) provided blood samples before (October 2019 to March 2020; air quality index = 37) and during (August 2020; air quality index = 80) a major wildfire. Exposure samples were collected 11 days (range, 10-12 days) after continuous exposure to wildfire smoke. We determined alterations in 506 proteins, including zonulin family peptide (ZFP); immune cell phenotypes by cytometry by time of flight (CyTOF); and their interrelationship using a correlation matrix. Results: Targeted proteomic analyses (n = 15) revealed a decrease of spondin-2 and an increase of granzymes A, B, and H, killer cell immunoglobulin-like receptor 3DL1, IL-16, nibrin, poly(ADP-ribose) polymerase 1, C1q TNF-related protein, fibroblast growth factor 19, and von Willebrand factor after 11 days' average continuous exposure to smoke from a large wildfire (P < .05). We also observed a large correlation cluster between immune regulation pathways (IL-16, granzymes A, B, and H, and killer cell immunoglobulin-like receptor 3DL1), DNA repair [poly(ADP-ribose) 1, nibrin], and natural killer cells. We did not observe changes in ZFP levels suggesting a change in epithelial barriers. However, ZFP was associated with immune cell phenotypes (naive CD4+, TH2 cells). Conclusion: We observed functional changes in critical immune cells and their proteins during wildfire smoke exposure. Future studies in larger cohorts or in firefighters exposed to wildfire smoke should further assess immune changes and intervention targets.

Autosomic Dominant Tubulo Interstitial Kidney Disease: Case Report of a New Variant of the UMOD Gene.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a low-prevalence pathology mainly associated with pathogenic variants of the UMOD gene. It is characterized by the progressive deterioration of renal function, associated with hyperuricemia and accompanied by a family history of gout or hyperuricemia. Often, clinical variability and a lack of molecular testing results in diagnostic failure to determine the ADTKD-UMOD association. Case presentation: We describe the case of a 14-year-old male who presented to the nephrology service with hyperuricemia, renal ultrasonographic changes, and progression to chronic kidney disease in 4 years. He had a family history of hyperuricemia. A probable genetic disease with an autosomal dominant inheritance pattern was considered, confirmed by the presence of a probably pathogenic variant of the UMOD gene, not previously reported in the literature. Conclusion: The investigation of this case led to the identification of a new variant in the UMOD gene, broadening the spectrum of known variants for ADTKD-UMOD. In addition, in this case, a comprehensive anamnesis, that takes into account family history, was the key point to carry out genetic tests that confirmed the diagnosis suspicion. Directed Genetic tests are currently an essential diagnostic tool and should be performed as long as they are available and there is an indication to perform them.

Air pollution and pregnancy.

Increased fossil fuel usage and extreme climate change events have led to global increases in greenhouse gases and particulate matter with 99% of the world's population now breathing polluted air that exceeds the World Health Organization's recommended limits. Pregnant women and neonates with exposure to high levels of air pollutants are at increased risk of adverse health outcomes such as maternal hypertensive disorders, postpartum depression, placental abruption, low birth weight, preterm birth, infant mortality, and adverse lung and respiratory effects. While the exact mechanism by which air pollution exerts adverse health effects is unknown, oxidative stress as well as epigenetic and immune mechanisms are thought to play roles. Comprehensive, global efforts are urgently required to tackle the health challenges posed by air pollution through policies and action for reducing air pollution as well as finding ways to protect the health of vulnerable populations in the face of increasing air pollution.